Regional requirements for Dishevelled signaling during Xenopus gastrulation: separable effects on blastopore closure, mesendoderm internalization and archenteron formation

During amphibian gastrulation, the embryo is transformed by the combined actions of several different tissues. Paradoxically, many of these morphogenetic processes can occur autonomously in tissue explants, yet the tissues in intact embryos must interact and be coordinated with one another in order to accomplish the major goals of gastrulation: closure of the blastopore to bring the endoderm and mesoderm fully inside the ectoderm, and generation of the archenteron. Here, we present high-resolution 3D digital datasets of frog gastrulae, and morphometrics that allow simultaneous assessment of the progress of convergent extension, blastopore closure and archenteron formation in a single embryo. To examine how the diverse morphogenetic engines work together to accomplish gastrulation, we combined these tools with time-lapse analysis of gastrulation, and examined both wild-type embryos and embryos in which gastrulation was disrupted by the manipulation of Dishevelled (Xdsh) signaling. Remarkably, although inhibition of Xdsh signaling disrupted both convergent extension and blastopore closure, mesendoderm internalization proceeded very effectively in these embryos. In addition, much of archenteron elongation was found to be independent of Xdsh signaling, especially during the second half of gastrulation. Finally, even in normal embryos, we found a surprising degree of dissociability between the various morphogenetic processes that occur during gastrulation. Together, these data highlight the central role of PCP signaling in governing distinct events of Xenopus gastrulation, and suggest that the loose relationship between morphogenetic processes may have facilitated the evolution of the wide variety of gastrulation mechanisms seen in different amphibian species

Psychological well-being and diabetes-related distress in states of type 2 diabetes in the first multi-national Diabetes Attitudes, Wishes and Needs (DAWN) Study

Purpose. To examine well-being and diabetes-related distress across several common states differentiated in the course of type 2 diabetes. Material and methods. Random samples of adults with type 2 diabetes were obtained from multiple co- untries in the first DAWN (Diabetes Attitudes, Wishes, and Needs) Study (n = 3432). All data were obtained during structured interviews. Criteria for defining states of diabetes included time since diagnosis of diabetes, the timing and nature of anti-hyperglycaemic medication regimens, and the timing and number of complications.  Results. Duration of diabetes closely corresponded to a set of typical states based on the criteria. Using analysis of covariance to control for confounding factors, diabetes-related distress and psychological well-being were significantly (p &lt; 0.05) worse for persons with diabetes with more complications and more intense medication regimens. Longer duration of insulin use was significantly associated with more diabetes-related distress. Worse distress and well-being were significantly associated with the accumulation of complications over time, but were more strongly associated with recently diagnosed complications than with more distally diagnosed complications.  Conclusions. Well-being and distress varied over sta- tes as defined by the nature and timing of diagnoses and medications. The observed patterns were more complex than a linear model of disease staging would suggest. Purpose. To examine well-being and diabetes-related distress across several common states differentiated in the course of type 2 diabetes. Methods. Random samples of adults with type 2 diabetes were obtained from multiple countries in the DAWN (Diabetes Attitudes, Wishes, and Needs) Study (n = 3432). All data were obtained during structured interviews. Criteria for defining states of diabetes included time since diagnosis of diabetes, the timing and nature of anti-hyperglycaemic medication regimens, and the timing and number of complications. Results: Duration of diabetes closely corresponded to a set of typical states based on the criteria. Using analysis of covariance to control for confounding factors, diabetes-related distress and psychological well-being were significantly (p < 0.05) worse for persons with diabetes with more complications and more intense medication regimens. Longer duration of insulin use was significantly associated with more diabetes-related distress. Worse distress and well-being were significantly associated with the accumulation of complications over time, but were more strongly associated with recently diagnosed complications than with more distally diagnosed complications. Conclusions: Well-being and distress varied over states as defined by the nature and timing of diagnoses and medications. The observed patterns were more complex than a linear model of disease staging would suggest

Motivation: key to a healthy lifestyle in people with diabetes? Current and emerging knowledge and applications

Aim Motivation to take up and maintain a healthy lifestyle is key to diabetes prevention and management. Motivations are driven by factors on the psychological, biological and environmental levels, which have each been studied extensively in various lines of research over the past 25 years. Here, we analyse and reflect on current and emerging knowledge on motivation in relation to lifestyle behaviours, with a focus on people with diabetes or obesity. Structured according to psychological, (neuro‐)biological and broader environmental levels, we provide a scoping review of the literature and highlight frameworks used to structure motivational concepts. Results are then put in perspective of applicability in (clinical) practice. Results Over the past 25 years, research focusing on motivation has grown exponentially. Social–cognitive and self‐determination theories have driven research on the key motivational concepts ‘self‐efficacy’ and ‘self‐determination’. Neuro‐cognitive research has provided insights in the processes that are involved across various layers of a complex cortical network of motivation, reward and cognitive control. On an environmental – more upstream – level, motivations are influenced by characteristics in the built, social, economic and policy environments at various scales, which have provided entry points for environmental approaches influencing behaviour. Conclusions Current evidence shows that motivation is strongly related to a person's self‐efficacy and capability to initiate and maintain healthy choices, and to a health climate that supports autonomous choices. Some approaches targeting motivations have been shown to be promising, but more research is warranted to sustainably reduce the burden of diabetes in individuals and populations

Type A behavior and risk of all-cause mortality, CAD, and CAD-related mortality, in a type 1 diabetes population: 22 years of follow-up in the Pittsburgh Epidemiology of Diabetes Complications Study

Objective To determine whether type A behavior predicts all cause mortality and incident coronary artery disease (CAD) in a type 1 diabetes population. Research Design and Methods Twenty-two year follow-up data from the Pittsburgh Epidemiology of Diabetes Complications (EDC) study of childhood onset type 1 diabetes were analyzed for the 506 participants who completed the Bortner Rating Scale (measuring type A myocardial infarction as determined by hospital records/ Q waves on ECG, CAD death behavior) and Beck’s Depression Inventory (BDI) at baseline (1986-1988). CAD comprised (determined by a mortality classification committee), angiographic stenosis, ischemic ECG and angina. Results There were 128 deaths (25.3%) during follow-up. Univariate analysis showed an inverse relationship between Bortner scores and all cause mortality (p=0.01) which remained significant after allowing for age, sex, duration, HbA1c, education, smoking, BMI, and physical activity (p=0.03). However, the addition of BDI scores attenuated the relationship (p=0.11) with a significant interaction (p=0.03) such that any protective effect against mortality was limited among individuals with lower BDI scores (bottom 3 quintiles) (p=0.07), while no effect was seen in those with higher BDI (p=0.97). Bortner scores showed only a borderline association with incident CAD (p=0.09). Conclusions Those with higher type A behavior have lower all-cause mortality in our type 1 diabetes population, an effect that interacts with depressive symptomatology such that it is only operative in those with low BDI scores. Further research should focus on understanding this interaction

Challenging Social Cognition Models of Adherence:Cycles of Discourse, Historical Bodies, and Interactional Order

Attempts to model individual beliefs as a means of predicting how people follow clinical advice have dominated adherence research, but with limited success. In this article, we challenge assumptions underlying this individualistic philosophy and propose an alternative formulation of context and its relationship with individual actions related to illness. Borrowing from Scollon and Scollon’s three elements of social action – “historical body,” “interaction order,” and “discourses in place” – we construct an alternative set of research methods and demonstrate their application with an example of a person talking about asthma management. We argue that talk- or illness-related behavior, both viewed as forms of social action, manifest themselves as an intersection of cycles of discourse, shifting as individuals move through these cycles across time and space. We finish by discussing how these dynamics of social action can be studied and how clinicians might use this understanding when negotiating treatment with patients

Elevated Depression Symptoms, Antidepressant Medicine Use, and Risk of Developing Diabetes During the Diabetes Prevention Program

OBJECTIVE—To assess the association between elevated depression symptoms or antidepressant medicine use on entry to the Diabetes Prevention Program (DPP) and during the study and the risk of developing diabetes during the study. RESEARCH DESIGN AND METHODS—DPP participants (n = 3,187) in three treatment arms (intensive lifestyle [ILS], metformin [MET], and placebo [PLB]) completed the Beck Depression Inventory (BDI) and reported their use of antidepressant medication at randomization and throughout the study (average duration in study 3.2 years). RESULTS—When other factors associated with the risk of developing diabetes were controlled, elevated BDI scores at baseline or during the study were not associated with diabetes risk in any arm. Baseline antidepressant use was associated with diabetes risk in the PLB (hazard ratio 2.25 [95% CI 1.38–3.66]) and ILS (3.48 [1.93–6.28]) arms. Continuous antidepressant use during the study (compared with no use) was also associated with diabetes risk in the same arms (PLB 2.60 [1.37–4.94]; ILS 3.39 [1.61–7.13]), as was intermittent antidepressant use during the study in the ILS arm (2.07 [1.18–3.62]). Among MET arm participants, antidepressant use was not associated with developing diabetes. CONCLUSIONS—A strong and statistically significant association between antidepressant use and diabetes risk in the PLB and ILS arms was not accounted for by measured confounders or mediators. If future research finds that antidepressant use independently predicts diabetes risk, efforts to minimize the negative effects of antidepressant agents on glycemic control should be pursued

A qualitative study of pain and related symptoms experienced by people with Ehlers-Danlos syndromes

IntroductionIndividuals with Ehlers-Danlos syndromes (EDS) often have complex and multi-faceted symptoms across the lifespan. Pain and the related symptoms of fatigue and sleep disorders are common. The objective of this qualitative study was to understand how participants manage their pain and related symptoms.MethodsThe design was a qualitative thematic content analysis. Twenty-eight interviews were conducted to collect data from individuals who were participants in a prior quantitative longitudinal study. A semi-structured interview guide was designed to focus on and understand the trajectory of pain, sleep, fatigue, and general function. The interview continued with questions about coping mechanisms and obstacles to maintaining a sense of well-being.ResultsSymptoms reported by participants were widespread and often interwoven. Pain was universal and often resulted in fatigue and disordered sleep which impacted physical function. Most participants reported that their symptoms worsened over time. Participants reported a wide range of effective interventions and most reported developing self-care strategies to adapt to their disabilities/limitations. Solutions included complementary interventions discovered when conventional medicine was unsuccessful. Very few relied on a “system” of health care and instead developed their own strategies to adapt to their disabilities/limitations.DiscussionEDS symptoms are often debilitating, and their progression is unknown. For most participants, symptoms worsened over the time. Even though participants in our study, by experience, were self-reliant, the importance of knowledgeable medical providers to help guide self-care should be emphasized

A Modular Design for the 56 Variants of the Short Straight Section in the Arcs of the Large Hadron Collider (LHC)

The 360 Short Straight Sections (SSS) necessary for the eight arcs of the LHC machine have to fulfil different requirements. Their main function is to house the lattice two-in-one superconducting quadrupole and various correction magnets, all operating at 1.9 K in a superfluid helium bath. The magnetic and powering schemes of the arcs and the fact that the two proton beams alternate between the inner and outer magnet channels impose 24 different combinations of magnet assemblies, all housed in an identical helium enclosure. The cryogenic architecture of the LHC machine is based on cryogenic loops spanning over one half-cell (53 m) for the 4.6-20 K circuit, over a full cell (107 m) for the 1.9 K circuits, up to the full arc (about 2.3 km) for the shield cooling line. This cryogenic layout, when superimposed to the magnetic scheme, further complicated by the cryostat insulation vacuum sectorisation every 2 cells, creates additional assembly variants, up to a total number of 56. The required flexibility in the manufacture and assembly, as well as economic considerations, have led to a modular design for the different SSS components and sub-assemblies. This modularity allows to "specialise" the SSS at the latest possible assembly step of the "just in time" production line. This paper presents the conceptual design considerations to achieve this modularity, the SSS design retained for the series manufacture, and the assembly procedures recently validated on a prototype program at CERN

Motivation: key to a healthy lifestyle in people with diabetes? Current and emerging knowledge and applications

Aim Motivation to take up and maintain a healthy lifestyle is key to diabetes prevention and management. Motivations are driven by factors on the psychological, biological and environmental levels, which have each been studied extensively in various lines of research over the past 25 years. Here, we analyse and reflect on current and emerging knowledge on motivation in relation to lifestyle behaviours, with a focus on people with diabetes or obesity. Structured according to psychological, (neuro‐)biological and broader environmental levels, we provide a scoping review of the literature and highlight frameworks used to structure motivational concepts. Results are then put in perspective of applicability in (clinical) practice. Results Over the past 25 years, research focusing on motivation has grown exponentially. Social–cognitive and self‐determination theories have driven research on the key motivational concepts ‘self‐efficacy’ and ‘self‐determination’. Neuro‐cognitive research has provided insights in the processes that are involved across various layers of a complex cortical network of motivation, reward and cognitive control. On an environmental – more upstream – level, motivations are influenced by characteristics in the built, social, economic and policy environments at various scales, which have provided entry points for environmental approaches influencing behaviour. Conclusions Current evidence shows that motivation is strongly related to a person's self‐efficacy and capability to initiate and maintain healthy choices, and to a health climate that supports autonomous choices. Some approaches targeting motivations have been shown to be promising, but more research is warranted to sustainably reduce the burden of diabetes in individuals and populations